EXPANDED METHODS FOR ONLINE PUBLICATION

The San Antonio Heart Study: The San Antonio Heart Study is a population-based study of type 2 diabetes and cardiovascular disease in Mexican Americans and Non-Hispanic whites of San Antonio, Texas. A person was Mexican American if he had 3 or more grandparents of Mexican origin, or both parents were born in Mexico and his self-declared ethnic identity did not specifically rule out a Mexican origin. A person was non-Hispanic white if he had 3 or more grandparents of non-Hispanic white ethnic background (e.g., Czech, Irish, Italian, Greek).(8) Participants were enrolled in two phases. From January 1979 to December 1982 (phase 1) and from January 1984 to December 1988 (phase 2), we randomly selected households from low-income barrios, middle-income transitional neighborhoods, and high-income suburbs. All men and nonpregnant women aged 25 to 64 years who resided in the randomly sampled households were eligible to participate. A total of 5,158 subjects completed phases 1 and 2 (the overall response rate was 65.3%). Of these, 2343 Mexican Americans and 1339 non-Hispanic whites returned for follow-up (71.4%): those in phase 1 between October 1987 and November 1990, and those in phase 2 between October 1991 and October 1996. In the analysis, we used the data from these follow-up periods, because the mean age of participants at that time was closer to the mean ages of those in studies in Mexico City and Spain. Detailed descriptions have been published previously.(9-11)

The Mexico City Diabetes Study: The Mexico City Diabetes Study is a population-based study of cardiovascular risk factors in both diabetic and nondiabetic men and women from Mexico City. The study site consisted of six low-income neighborhoods, each one corresponding to one census tract. A complete household enumeration was performed in each neighborhood between November 1989 and February 1990, and 3,505 study-eligible individuals aged 35- to 64-years were identified. A total of 2,282 men and nonpregnant women completed the survey (the overall response rate was 65.0%). Detailed descriptions of this study have been published previously.(11)

Acquisition of data in San Antonio and Mexico City: Both studies were approved by the Institutional Review Board of the University of Texas Health Science Center at San Antonio, and the Mexico City Diabetes Study was also approved by the Centro de Estudios en Diabetes in Mexico City. All subjects gave informed consent. Both studies used identical protocols with standardized and joint training for medical staff. A metallic tape was used to measure the waist circumference at the level of the umbilicus. Plasma glucose was measured by a glucose oxidase method. A 75-g oral glucose load (Orangedex; Custom Laboratories, Baltimore, MD) was administered to determine 2-hour plasma glucose level.

The Spanish Insulin Resistance Study: The Spanish Insulin Resistance Study was designed as a cross-sectional, population-based study of the prevalence of type 2 diabetes and cardiovascular risk factors. It was conducted in seven towns across Spain (Arévalo, Talavera de la Reina, Guadalajara, La Coruña, Avilés, Vic, Alicante, and Mérida) from March 1995 to April 1998. The overall population of these towns was 831,674 inhabitants ranging from 7,359 to 274,577.(12) From a targeted population of 348,980 inhabitants aged 34 to 69 years, initial interview was obtained on 3,172 men and nonpregnant women. Of those, 121 (3.8%) were excluded because of one or more of the following criteria: abdominal hernia, overt heart or hepatic failure, surgery during the previous year, weight changes above 5 kg within the previous 6 months, or being institutionalized. Complete physical examination and fasting blood samples were obtained on 2,949 participants, and 2-hour blood specimens were available on 2,123 participants (66.9% of the target population).

Acquisition of data in Spain: Survey procedures were adapted from the WHO MONICA protocol.(13) All participants gave informed consent. One of the investigators (S.H.) of both, the San Antonio Heart Study and Mexico City Diabetes Study was a consultant in the design of the Spanish Insulin Resistance Study. However, there was not medical staff cross training. Waist circumference was measured at the level of the umbilicus. Blood specimens were obtained after a 12-hour fast for determination of plasma glucose (Boerhinger Mannheim, Indianapolis, IN). An oral glucose tolerance test was performed with a 75-g oral glucose load challenge to assess the 2-hour plasma glucose concentration.

Definition of variables: In all three studies, the definition of variables was identical. Educational attainment was measured as the highest number of years of schooling completed. In the analysis, educational attainment was treated as a dichotomous variable: having vs. not having obtained a high school diploma. Overall adiposity was assessed by body mass index, and central fat distribution by waist circumference. Alcohol consumption was calculated as the number of drinks of alcohol consumed per week. Current smoking was assessed by interview. Systolic (first-phase) and diastolic blood pressures (fifth-phase) were measured to the nearest even digit with the participant in the sitting position. Both, systolic and diastolic blood pressures were reported as the mean of the first and second blood pressure readings. For the diagnosis of hypertension, we followed the indications of ‘The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V)’.(14) Subjects with systolic blood pressure ³ 140 mm Hg or diastolic blood pressure ³ 90 mm Hg. Subjects with history of hypertension who were currently treated with antihypertensive medications were considered to have hypertension. We followed ‘the 1997 Recommendations from the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.(15) Type 2 diabetes was defined as fasting plasma glucose level ³ 7.0 mmol/l and/or 2-hour glucose ³ 11.1 mmol/l. Diabetic subjects taking oral antidiabetic medications, or those taking insulin with body mass index > 27 and age at onset older than 30 years, were considered to have type 2 diabetes. In non-diabetic subjects, impaired fasting glucose was defined as fasting plasma glucose ³ 6.1 mmol/l and <7.0 mmol/l, and impaired glucose tolerance as 2-hour glucose level ³ 7.8 mmol/l and < 11.1 mmol/l.